Chicago, IL—A new high-intensity genomic sequencing strategy (developed by Grail Inc) detects circulating tumor DNA (ctDNA) at a high rate. The new approach is a major improvement on previous tests using ctDNA, which focus on a limited number of driver mutations to inform treatment strategies for metastatic disease or to monitor disease burden. The new test offers ultra-deep sequencing with a broad genomic coverage, but it is not ready for prime time to detect occult cancer. At present, the test is a research platform and is not commercially available.
“This approach offers an unprecedented combination of breadth and depth, covering about 508 genes and yielding 100 times more data than other approaches,” said lead investigator Pedram Razavi, MD, PhD, Medical Oncologist, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York City, during the 2017 American Society of Clinical Oncology (ASCO) meeting.
“Our findings show that high-intensity ctDNA sequencing is possible and may provide invaluable information for clinical decision-making, potentially without the need for tumor tissue samples. The ultimate goal would be to detect cancer in early, treatable stages,” he told attendees at a press conference at ASCO 2017.
At the meeting, Dr Razavi presented the results of a concordance study in 124 patients with metastatic breast cancer, non–small-cell lung cancer, or castration-resistant prostate cancer. Tumor tissue was analyzed using MSK-IMPACT, a 410-gene diagnostic test that provides detailed genetic information about the tumor. In blood samples, the plasma was separated from the blood cells. The cell-free DNA was extracted from the plasma, and separately, the genomes of white blood cells were then sequenced using the high-intensity 508-gene sequencing assay.
Comparing plasma and tissue samples, the new test was able to detect 89% of genetic changes that had been identified with regular tumor biopsy and 76% of “actionable” mutations amenable to currently available targeted therapy.
“A high level of concordance was seen for variants between plasma and tissue, providing strong evidence for high rates of tumor DNA detection in plasma,” Dr Razavi explained. “The breadth of detected variants in plasma ctDNA enables greater insight into tumor biology, including the first exploration of mutational signature analysis in plasma,” he added.
Experts Comment on Early Data
At the press conference, ASCO experts agreed that this technology is still in early days.
“We continue to see promising reports about the possible uses of circulating tumor DNA analysis. While this approach has a way to go before it becomes a proven technology for early cancer detection, this research is an important first step,” said John V. Heymach, MD, PhD, Chairman, Department of Thoracic/Head and Neck Medical Oncology, M.D. Anderson Cancer Center, Houston.
“These data are important, but we are a long way from using liquid biopsies for detecting cancers,” agreed ASCO expert Sumanta K. Pal, MD, Co-Director, Kidney Cancer Program, City of Hope Comprehensive Cancer Center, Duarte, CA.